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01-02-2011 | Original Article

Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1

Authors: Mariana Ferreira, Alessandra Torraco, Teresa Rizza, Fabiana Fattori, Maria Chiara Meschini, Cinzia Castana, Nancy E. Go, Frank E. Nargang, Margarida Duarte, Fiorella Piemonte, Carlo Dionisi-Vici, Arnaldo Videira, Laura Vilarinho, Filippo M. Santorelli, Rosalba Carrozzo, Enrico Bertini

Published in: Neurogenetics | Issue 1/2011

Abstract

We present clinical, neuroimaging, and molecular data on the identification of a new homozygous c.1783A>G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy, a clinical and neuroradiological entity originally related to unknown defects of the mitochondrial energy metabolism. In both sibs, the muscle biopsy showed severe reduction of complex I enzyme activity, which was not obvious in fibroblasts. We also observed complex I dysfunction in a Neurospora crassa model of the disease, obtained by insertional mutagenesis, and in patient fibroblasts grown in galactose. Altogether, these results indicate that the NDUFS1 mutation is responsible for the disease and complex I deficiency. Clinical presentation of complex I defect is heterogeneous and includes an ample array of clinical phenotypes. Expanding the number of allelic variants in NDUFS1, our findings also contribute to a better understanding on the function of complex I.

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Title: Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1
Authors: Mariana Ferreira
Alessandra Torraco
Teresa Rizza
Fabiana Fattori
Maria Chiara Meschini
Cinzia Castana
Nancy E. Go
Frank E. Nargang
Margarida Duarte
Fiorella Piemonte
Carlo Dionisi-Vici
Arnaldo Videira
Laura Vilarinho
Filippo M. Santorelli
Rosalba Carrozzo
Enrico Bertini
Publication date: 01-02-2011
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 1/2011
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-010-0265-2

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Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1

Abstract

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Abstract

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